High Salt Activates Dendritic Cells to Promote Hypertension

• DOI: 10.1096/fasebj.30.1_supplement.1216.5
• Publication Date: 2023-11-26T16:34:18Z
• Authors: Jason David Foss; Natalia Barbaro; Liang Xiao; Sergey Dikalov; David G Harrison; Annet Kirabo
• Keywords: P22phox; CD80; CD86

Both inflammation and dietary salt intake have been implicated in the pathogenesis of hypertension. We previously shown that formation immunogenic isoketal‐protein adducts dendritic cells (DCs) plays an important role development experimental Recently, it has can accumulate interstitial space promote inflammation. In current study, we tested hypothesis exposure to high drives DCs toward activated state, leading production isoketals promotion To test this hypothesis, mouse splenic were cultured media with either normal (NS, 150 mM NaCl) or (HS, 190 for 24 hours. Exposure HS caused a 2‐fold increase superoxide compared NS. This was NADPH oxidase‐dependent since incubation gp91ds‐tat peptide prevented increase. also led activation markers CD80 CD86, doubled number containing adducts. Moreover, exposed but not NS drove proliferation both CD4 + (5198.2±2398.6 vs. 15.3±7.1 proliferated cells, p<0.01) CD8 (25381.6±9495.6 9.8±4.1 T cells. None these effects mediated by increased osmolality as addition mannitol (80 mM) had no effect. Western blots protein extracts from indicated all subunits (p47phox, p22phox, gp91phox p67phox) HS, inhibition serum‐and‐glucocorticoid‐inducible kinase‐1 (SGK1). additional experiments, mice received adoptive transfer hours (n = 5); plus SGK1 inhibitor, GSK 650394 (HS+GSK, n 5) isoketal scavenger, 2‐hydroxybenzylamine (HS+2‐HOBA, n=5). Mice then implanted radiotelemeters measure arterial pressure. Following recovery two days baseline, subcutaneous osmotic minipumps administration generally sub‐pressor dose angiotensin II (140 ng/kg/min). blood pressure DCs, whereas mean significantly (14 ± 4 mmHg, p<0.05) one week angiotensinogen infusion salt‐activated DCs. The pro‐hypertensive effect on completely blocked scavenging during their exposure. Taken together, our data indicate be environment which exist states, likely involves oxidase cause become pro‐hypertensive. These studies define new pathway linking immune identify undefined process. Support Funding Information work is supported National Institutes Health grants R01HL039006, P01HL058000, P01HL095070, P01GM015431, R01HL108701, R01HL105294, VITA award HHSN268201400010C Strategically Focused Research Network Award American Heart Association.